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MRI confirms loss of blood–brain barrier integrity in a mouse model of disseminated candidiasis
Author(s) -
Navarathna Dhammika H. M. L. P.,
Munasinghe Jeeva,
Lizak Martin J.,
Nayak Debasis,
McGavern Dorian B.,
Roberts David D.
Publication year - 2013
Publication title -
nmr in biomedicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.278
H-Index - 114
eISSN - 1099-1492
pISSN - 0952-3480
DOI - 10.1002/nbm.2926
Subject(s) - candida albicans , blood–brain barrier , in vivo , meningoencephalitis , corpus albicans , biology , pathology , intravital microscopy , central nervous system , immunology , microbiology and biotechnology , medicine , neuroscience
Disseminated candidiasis primarily targets the kidneys and brain in mice and humans. Damage to these critical organs leads to the high mortality associated with such infections, and invasion across the blood–brain barrier can result in fungal meningoencephalitis. Candida albicans can penetrate a brain endothelial cell barrier in vitro through transcellular migration, but this mechanism has not been confirmed in vivo . MRI using the extracellular vascular contrast agent gadolinium diethylenetriaminepentaacetic acid demonstrated that integrity of the blood–brain barrier is lost during C . albicans invasion. Intravital two‐photon laser scanning microscopy was used to provide the first real‐time demonstration of C . albicans colonizing the living brain, where both yeast and filamentous forms of the pathogen were found. Furthermore, we adapted a previously described method utilizing MRI to monitor inflammatory cell recruitment into infected tissues in mice. Macrophages and other phagocytes were visualized in kidney and brain by the administration of ultrasmall iron oxide particles. In addition to obtaining new insights into the passage of C . albicans across the brain microvasculature, these imaging methods provide useful tools to study further the pathogenesis of C . albicans infections, to define the roles of Candida virulence genes in kidney versus brain infection and to assess new therapeutic measures for drug development. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.